Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS4149405 A
Publication typeGrant
Application numberUS 05/867,878
Publication dateApr 17, 1979
Filing dateJan 9, 1978
Priority dateJan 10, 1977
Publication number05867878, 867878, US 4149405 A, US 4149405A, US-A-4149405, US4149405 A, US4149405A
InventorsAnthony Ringrose
Original AssigneeBattelle, Centre De Recherche De Geneve
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Process for measuring the viscosity of a fluid substance
US 4149405 A
Abstract
The viscosity of a fluid material, e.g. a synthetic-resin composition, or the coagulation of blood or plasma monitored by placing a quantity of the fluid substance on a support, directing a beam of light upon the sample, detecting reflected light from the sample and vibrating the support at a given frequency and amplitude to disturb its surface. The reflected light detected is a function of the viscosity or the degree of coagulation.
Images(2)
Previous page
Next page
Claims(6)
I claim:
1. A process for measuring the viscosity of a fluid substance comprising the steps of:
placing a sample of the fluid substance whose viscosity is to be measured upon a support;
training a beam of light upon the sample on said support;
vibrating said support with said sample thereon to disturb the surface of the sample; and
measuring light reflected from said support, the measured reflected light being a function of the viscosity of said sample.
2. The process defined in claim 1 wherein the reflectivity from said sample is measured as a function of time to monitor the change in viscosity of said sample over a time period.
3. The process defined in claim 2 wherein said sample is a synthetic resin.
4. The process defined in claim 2 wherein said sample includes coagulatable blood components, the change in viscosity of said sample being a function of the coagulation of said component.
5. A process for detecting the coagulation of blood components in a fluid substance, said process comprising the steps of:
placing a sample of said fluid substance on a support;
training a beam of light on said sample on said support;
vibrating said sample to disturb the surface thereof at a predetermined frequency and amplitude;
measuring reflected light from said surface as a function of time; and
establishing as the coagulation time of said sample the period of onset of measurement of the reflected light to incipient decrease in the amplitude of the light reflected from said surface.
6. The process defined in claim 5, further comprising monitoring the evolution of coagulation subsequent to said coagulation time by continuing to monitor reflected light from said surface after said coagulation time.
Description
FIELD OF THE INVENTION

The present invention relates to the determination of the viscosity of a fluid material and, more particularly, to a method of and a device for determining the viscosity of fluid materials or the coagulation of blood or blood plasma.

BACKGROUND OF THE INVENTION

In order to measure the viscosity of a fluid substance a certain deformation force can be exerted on this substance and the resistance offered by the substance can be measured. Although blood coagulation is not strictly speaking a viscosity, its measurement can be closely paralleled with that of a viscosity measurement in that a sample is subjected to a particular deformation force and the deformation is observed.

Blood coagulation is the result of a particularly complex biochemical process which is caused according to the type by different combinations of a plurality of components called "factors" contained in the blood. At the present twelve factors are said to play a role in this process.

Interactions between these factors lead in the case of normal blood to the formation of a filamentary network called fibrin, the production of which is characteristic of coagulation. The purpose of the coagulometer is to detect the exact instant of the formation of this network.

The coagulation of blood in the laboratory has been initiated heretofore by several different methods each relying on the use of a respective different group of factors as a function of the information desired. The choice of methods allows one to eliminate or to accentuate the action of different factors in the blood. The sample is either whole blood or plasma. In most cases this blood or this plasma is prevented from coagulating by the addition of an anticoagulant to the fresh blood, this anticoagulant being constituted by a solution of trisodium citrate or sodium oxalate. The plasmas of blood treated with one or the other of these solutions is called "citrated plasma" or "oxalated plasma". These solutions have the effect of eliminating Ca++ ions from the blood, following which the plasma is separated by centrifuging.

Most coagulometers in use read out the time of incipient appearance of the fibrin. There is a wide variety of electromechanical measuring devices for coagulation in use in laboratories. Many of these devices are rather imprecise and disturb the blood during the coagulation process. Most require a relatively large quantity of blood as the sample and only measure a single point in the coagulation process, not allowing one to measure the evolution of this process. As a rule these devices cannot be used for all coagulation measurements.

Although in many cases the numerical measurement of the process is sufficient, for example for monitoring the administration of anticoagulant substances, it is occasionally useful to know more about the entire evolution of the process, for instance to advance research in this field and to allow more precise diagnoses.

There are so-called "thromboelastographs" which record coagulation graphs. As a result of their complexity such devices cannot be used for running analyses.

The very newest devices meant for use in analytic laboratories are photometric devices which measure the absorption by the sample of a light beam. The formation of fibrin, which is characteristic of coagulation, increasingly diffuses the light of the beam. The remaining light, and as a result the absorbance of the sample, is measured by a photoelectric cell placed across from the source of light, this cell and this source being to opposite sides of the sample.

This analysis system has two advantages over those which have existed to date. No object touches the sample during analysis, and the signal picked up is analog and usable for drawing a graph indicating the evolution of the process.

Nonetheless the basic principle on which this apparatus operates is incompatible with certain analytical methods or for certain pathogenic forms of plasma or blood. The analysis of whole blood is effectively ruled out by the fact that such blood is too opaque. This detection method is in addition poorly adapted for measuring the coagulation of exalted plasmas because they are disturbed during the process. For certain diseases, lipemia for example, the plasma is cloudy, thereby falsifying the measurement. Finally the evaluation of the formation of fibrin is very temporary with such a device.

There are fields other than hematology wherein the measurement of viscosity itself sometimes poses problems that are only inadequately solved, in particular measurement of the viscosity of non-Newtonian liquids. As is known this viscosity is mainly a function of the speed of deformation of these liquids. As a result their measurement can only be made by applying different deformation speeds at a constant temperature so that the viscosity is a curve illustrating a function of these speeds of deformation. In any case the known viscosimeters hardly allow one to measure viscosities at deformation speeds less than 1 sec-1. On the other hand the determination of the viscosity at a very small deformation speed is of interest because it allows one to determine a molecular weight of a polymer.

OBJECT OF THE INVENTION

An object of the present invention is to overcome at least in part the above-given disadvantages.

SUMMARY OF THE INVENTION

The above and other objects are attained, in accordance with the invention, in a process for measuring the viscosity of a fluid substance, in particular the evolution of blood coagulation, as a function of time, in that a sample to be measured is placed on a support, a beam of light is directed against the free surface of this sample, the sample is vibrated at a given frequency and amplitude so as to disturb its free surface and the light reflected by a portion of this surface, which is characteristic of the viscosity of this sample, is measured.

BRIEF DESCRIPTION OF THE DRAWING

The above and other objects, features and advantages of the present invention will become more readily apparent from the following description, reference being made to the accompanying drawing in which:

FIG. 1 is a side-elevational view of an apparatus for carrying out the method of the present invention;

FIG. 2 is a diagram illustrating the functioning of the apparatus and the treatment of the signal obtained;

FIGS. 3-5 are three graphs of tests of coagulation of three different samples; and

FIG. 6 is a graph showing the viscosity of a polymer as a function of the deformation speed which is applied to it.

SPECIFIC DESCRIPTION

The apparatus of FIG. 1 comprises a support 1 carrying an electromagnet 2 and an arm 3 pivoted about an axle 4 and whose degree of motion is determined by an abutment 5 spaced from the electromagnet 2. A return spring 6 biases the arm 3 against the abutment 5. This arm 3 carries a plate 7 adapted to carry the sample. Preferably this plate is formed of a synthetic-resin material such as Delrin rather than glass whose influence on the coagulation process is known.

A light source 8 is aimed at the center of the plate and a photoelectric receiver 9 is placed at a location determined by the reflected light. As will be seen below when the arm 3 is at rest, the receiver 9 can either receive the light reflected from the surface of the sample carried by the plate 7 or receive no light.

The principle on which the method is based consists of forming on the plate 7 a drop of the sample calibrated in such a manner that its shape can be reproduced. This sample is either formed of whole blood or of plasmas and an appropriate reagent. When the sample is placed on the plate, this plate is vibrated and the surface of the drop is irradicated. The vibrations which deform the surface of this drop disturb the light reflected by this surface. As soon as coagulation starts the influence of the vibrations on the surface of this drop diminish progressively so that the amount of reflected light received by the receiver 9 varies until the coagulation is complete. If the receiver 9 is normally positioned in the path of the beam of reflected light the quantity of light received will vary from a minimum to a maximum between the start and the end of the process period. However if the receiver 9 is normally outside of this path, the vibrations communicated to the drop of the sample before coagulation make the deformed surface of this drop reflect a part of the light toward the cell 9 and this quantity will decrease as the coagulation reduces the extent of the deformations transmitted to the surface of the drop.

In the arrangement shown in FIG. 1 the vibrations are caused by the electromagnet 2 fed by current pulses at a frequency from 2-4 Hz. These pulses vibrate the arm 3 urged by the spring 6 between the electromagnet 2 and the abutment 5.

Different tests have been carried out with the aid of equipment similar to that illustrated in FIG. 1 by treating the detected signals from the receiver 9 as shown in FIG. 2. In this diagram four series of signals a, b, c and d are shown. The signals a represent the feed pulses for the magnet 2, the signals b correspond to the excitation current of the photoelectric receiver 9 caused by the light received from a reflection of the light incident against the surface of the drop of the sample being vibrated as the electromagnet is excited. This current is proportional to the light received by the receiver and is as a result a function of the deformation of the surface of the drop of the sample being vibrated. The signal c corresponds to the integral of the signal b. The signal d corresponds to the value of the peaks of the signal c and is used for forming the curves of FIGS. 3-5.

The tests carried out to evaluate the performance of this method consist in measuring the time of prothrombin of a citrated control sample sold commercially and whose normal prothrombin time is known.

In order to measure the coagulation with this method the plasma is heated to 37 C. 30 μl are pipetted onto the plate 7 also heated to 37 C. Then on this same plate 60 μl of a reagent are deposited, normally a solution of thromboplastine and calcium chloride which has been heated to 37 C. The addition of this reagent determines very exactly the time t0 corresponding to the start of measurement and to the start of the excitation of the electromagnet 2 by the train of pulses a (FIG. 2) which vibrates the plate 7. The signal treated as described above is fed to a recording instrument which traces a curve similar to that of FIG. 3. On this curve the prothrombin time is given by t1 which corresponds to the beginning of the formation of fibrin. Most of prior-art devices only allow determination of this time t1. The process according to the invention allows in addition the following of the evolution of the coagulation process until its end.

The diagram of FIGS. 4 and 5 show the use of this graphic analytical method for the coagulation process. The traph of FIG. 4 was traced by using the same control plasma as mentioned above, but diluted to 50% of artificial serum, whereas the graph of FIG. 4 corresponds to this same control plasma diluted to 75% of artificial serum. It can be seen that in these two cases not only does the time t1 vary as a function of the dilution of the plasma, but that the shape of the curve between t1 and t2 is very different. This shows that the process of the invention allows the detection in addition to the prothrombine time of the complete coagulation time which itself varies noticeably as a function of the density of the fibrin network which forms not only at its start but also during the process. It is of course possible to observe the process of coagulation by introducing other "factors" than the method described. In all these cases the same mechanical phenomena would produce the same effects independent of the intervening factors in the coagulation process.

In addition to certain advantages of the process already mentioned it is also important to point out that the plasma is subjected to minimal disturbances during the coagulation process. The detecting devices of the process do not contact the substance which is reacting. The measuring process according to the invention is usable for all known methods no matter what the nature of the sample to be analyzed. In the tests tried the quantity of the sample is particularly small. At the same time nothing prevents it from being reduced further, the critical problem then being only that of the precision of the pipetting. The results obtained can be given either in numerical form or in analog form or even in both of these forms. The apparatus necessary for carrying out the process is extremely simple.

In addition to measuring the evolution of sanguine coagulation, the process described above is also in interest for the measurement of the viscosity of non-Newtonian liquids. It is not considered possible to measure the viscosity for deformation speeds smaller than 1 sec-1 with known viscosimeters. Knowing the viscosity at small deformation speeds would, however, be important because it would allow one to determine the molecular weight of a polymer.

The process, according to the invention, produces an output which is a function of the forces dissipated in the liquid and, therefore, of its viscosity. The vibration to which the sample is subjected allows one to communicate to it a very small deformation speed. As seen in FIG. 6 which shows the viscosity curves of three polyethylenes it is possible to note that as the deformation speed D goes to zero the measured viscosity η corresponds practically to ηo. This means that it is possible with the process, according to the invention, to measure the viscosity ηo of a polymer.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3077764 *Oct 30, 1959Feb 19, 1963Standard Oil CoPour point instrument
US3650698 *Dec 4, 1969Mar 21, 1972Technicon CorpApparatus for the automatic determination of the coagulation, aggregation and or flocculation, or the like, rates of fluids, and novel reaction intensifying agent for use therewith
US3752443 *Dec 13, 1971Aug 14, 1973Technicon InstrMagnetic mixer
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5686661 *Jun 4, 1996Nov 11, 1997Mississippi State UniversityIn-situ, real time viscosity measurement of molten materials with laser induced ultrasonics
US6019735 *Aug 28, 1997Feb 1, 2000Visco Technologies, Inc.Viscosity measuring apparatus and method of use
US6077234 *Jun 23, 1998Jun 20, 2000Visco Technologies, Inc.In-vivo apparatus and method of use for determining the effects of materials, conditions, activities, and lifestyles on blood parameters
US6152888 *Sep 21, 1999Nov 28, 2000Visco Technologies, Inc.Viscosity measuring apparatus and method of use
US6193667Nov 15, 1999Feb 27, 2001Visco Technologies, Inc.Methods of determining the effect(s) of materials, conditions, activities and lifestyles
US6200277Nov 15, 1999Mar 13, 2001Visco Technologies, Inc.In-vivo apparatus and methods of use for determining the effects of materials, conditions, activities, and lifestyles on blood parameters
US6261244Aug 25, 1999Jul 17, 2001Visco Technologies, Inc.Viscosity measuring apparatus and method of use
US6322524Nov 12, 1999Nov 27, 2001Visco Technologies, Inc.Dual riser/single capillary viscometer
US6322525Feb 10, 2000Nov 27, 2001Visco Technologies, Inc.Method of analyzing data from a circulating blood viscometer for determining absolute and effective blood viscosity
US6402703May 18, 2000Jun 11, 2002Visco Technologies, Inc.Dual riser/single capillary viscometer
US6412336Jul 2, 2001Jul 2, 2002Rheologics, Inc.Single riser/single capillary blood viscometer using mass detection or column height detection
US6428488Jul 12, 2000Aug 6, 2002Kenneth KenseyDual riser/dual capillary viscometer for newtonian and non-newtonian fluids
US6450974Nov 8, 2000Sep 17, 2002Rheologics, Inc.Method of isolating surface tension and yield stress in viscosity measurements
US6484565Jul 2, 2001Nov 26, 2002Drexel UniversitySingle riser/single capillary viscometer using mass detection or column height detection
US6484566Nov 27, 2000Nov 26, 2002Rheologics, Inc.Electrorheological and magnetorheological fluid scanning rheometer
US6564618Jul 17, 2002May 20, 2003Rheologics, Inc.Electrorheological and magnetorheological fluid scanning rheometer
US6571608May 28, 2002Jun 3, 2003Rheologics, Inc.Single riser/single capillary viscometer using mass detection or column height detection
US6598465Jul 1, 2002Jul 29, 2003Rheologics, Inc.Electrorheological and magnetorheological fluid scanning rheometer
US6624435Dec 27, 2001Sep 23, 2003Rheologics, Inc.Dual riser/dual capillary viscometer for newtonian and non-newtonian fluids
US6732573Apr 22, 2002May 11, 2004Rheologics, Inc.Single riser/single capillary blood viscometer using mass detection or column height detection
US6745615Oct 9, 2001Jun 8, 2004Rheologics, Inc.Dual riser/single capillary viscometer
US6796168Sep 17, 2002Sep 28, 2004Rheologics, Inc.Method for determining a characteristic viscosity-shear rate relationship for a fluid
US6805674Jun 28, 2002Oct 19, 2004Rheologics, Inc.Viscosity measuring apparatus and method of use
US6845327 *Jun 8, 2001Jan 18, 2005Epocal Inc.Point-of-care in-vitro blood analysis system
US6907772Apr 23, 2004Jun 21, 2005Rheologics, Inc.Dual riser/single capillary viscometer
US7261861 *Apr 24, 2003Aug 28, 2007Haemoscope CorporationHemostasis analyzer and method
US7857761 *Apr 16, 2004Dec 28, 2010Drexel UniversityAcoustic blood analyzer for assessing blood properties
US7879615Jun 22, 2006Feb 1, 2011Coramed Technologies, LlcHemostasis analyzer and method
US8236568Jun 1, 2007Aug 7, 2012Coramed Technologies, LlcMethod for analyzing hemostasis
US20020040196 *Oct 9, 2001Apr 4, 2002Kenneth KenseyDual riser/single capillary viscometer
US20030148530 *Jun 8, 2001Aug 7, 2003Lauks Imants R.Point-of-care in-vitro blood analysis system
US20030158500 *Feb 13, 2003Aug 21, 2003Kenneth KenseyDecreasing pressure differential viscometer
US20040194538 *Apr 23, 2004Oct 7, 2004Rheologics, Inc.Dual riser/single capillary viscometer
US20040214337 *Apr 24, 2003Oct 28, 2004Hans KautzkyHemostasis analyzer and method
US20050015001 *Apr 16, 2004Jan 20, 2005Lec Ryszard M.Acoustic blood analyzer for assessing blood properties
US20070092405 *Jun 22, 2006Apr 26, 2007Haemoscope CorporationHemostasis Analyzer and Method
US20070224686 *Jun 1, 2007Sep 27, 2007Haemoscope CorporationMethod for Analyzing Hemostasis
US20070237677 *Jun 1, 2007Oct 11, 2007Haemoscope CorporationResonant Frequency Hemostasis Analyzer
EP1039295A2 *Mar 10, 2000Sep 27, 2000Holger BehnkSystem for measuring the coagulation of body fluids
EP1039295A3 *Mar 10, 2000Jul 11, 2001Holger BehnkSystem for measuring the coagulation of body fluids
EP1039296A1 *Mar 19, 1999Sep 27, 2000Holger BehnkSystem for measuring coagulation of bodily fluids
WO1999010724A2Aug 26, 1998Mar 4, 1999Visco Technologies, Inc.Viscosity measuring apparatus and method of use
WO1999066839A1Jun 22, 1999Dec 29, 1999Visco Technologies, Inc.In-vivo determining the effects of a pharmaceutical on blood parameters
WO2001036936A1Oct 12, 2000May 25, 2001Rheologics, Inc.Dual riser/single capillary viscometer
WO2001058356A2Feb 7, 2001Aug 16, 2001Rheologics, Inc.Method for determining absolute and effective blood viscosity
WO2001086255A1 *May 8, 2001Nov 15, 2001Trustees Of Tufts CollegeMethod and apparatus for determining local viscoelasticity
WO2002009583A2Jul 30, 2001Feb 7, 2002Rheologics, Inc.Apparatus and methods for comprehensive blood analysis, including work of, and contractility of, heart and therapeutic applications and compositions thereof
WO2003020133A2Jul 31, 2002Mar 13, 2003Rheologics, Inc.Method for determining the viscosity of an adulterated blood sample over plural shear rates
WO2006110963A1 *Apr 21, 2006Oct 26, 2006K.U.Leuven Research And DevelopmentMonitoring of the v1sco-elastic properties of gels and liquids
Classifications
U.S. Classification73/54.01, 356/39
International ClassificationG01N11/00, G01N33/86, G01N33/49
Cooperative ClassificationG01N33/4905, G01N11/00
European ClassificationG01N33/49B, G01N11/00
Legal Events
DateCodeEventDescription
Dec 2, 1988ASAssignment
Owner name: INTRACEL CORPORATION, C/O COTTLE CATFORD & CO., BA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:BATTELLE MEMORIAL INSTITUTE;REEL/FRAME:005001/0948
Effective date: 19880914